加味温胆汤对急性心肌梗死后心力衰竭大鼠心肌能量代谢和超微结构的影响

目的通过对急性心肌梗死后心力衰竭(HFMI)大鼠模型给药治疗,评估加味温胆汤对大鼠心肌能量代谢水平和心肌超微结构的影响。方法SD雄性大鼠随机分为两组,每组15只,造模组通过手术结扎冠状动脉左前降支造模,假手术组完成穿刺但并未结扎左前降支,术后饲养72 h,对两组大鼠进行慢性心衰评分并加以比较。将造模组15只大鼠分为3组,每组5只,中药组经口喂加味温胆汤,曲美他嗪组给予曲美他嗪溶液,对照组喂养生理盐水,给药4周后空腹抽取3组鼠尾静脉血,检测并比较各组大鼠心肌能量代谢因子:血清肌钙蛋白(cTnI)、心肌过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)水平;进行超声检查,测定并比较左室射血分数(LVEF);采集心肌样本进行HE染色(核染)和Masson染色(纤染),对心肌超微结构完整性进行评分。结果治疗4周后,中药组、曲美他嗪组大鼠LVEF数值均较治疗前显著增加(P<0.05),对照组与治疗前相比降低(P<0.05),但治疗后中药组大鼠LVEF数值高于曲美他嗪组(P<0.05);与治疗前相比,3组大鼠血清cTnI、PGC-1α表达水平差异有统计学意义(P<0.05),中药组<曲美他嗪组<对照组;治疗4周后,3组大鼠心肌超微结构完整性评分比较差异也具有统计学意义(P<0.05),中药组<曲美他嗪组<对照组。结论加味温胆汤对急性心肌梗死后心力衰竭大鼠的心肌能量代谢具有促进作用,对心肌超微结构的完整性具有保护作用,并能有效改善大鼠的心功能。     

加味葛根芩连汤联合常规治疗对重度湿热型溃疡性结肠炎患者的临床疗效

目的考察加味葛根芩连汤联合常规治疗对重度湿热型溃疡性结肠炎患者的临床疗效。方法82例患者随机分为对照组和观察组,每组41例,对照组给予常规治疗(美沙拉嗪、氢化可的松琥珀酸钠),观察组在对照组基础上加用加味葛根芩连汤,疗程4周。检测症状评分、中医证候疗效、肠镜Baron评分、膜屏障功能指标(HIF⁃1α、DAO、D⁃LA)、血清促炎因子(IL⁃2、IL⁃6、TNF⁃α、IFN⁃γ、CRP)、血清抗炎因子(IL⁃4、IL⁃10、IL⁃13)、免疫功能指标(CD3+、CD4+、CD8+、CD4+/CD8+、NK细胞)、凝血功能指标(FIB、APTT、PLT)、不良反应发生率变化。结果观察组总有效率较对照组升高(P<0.05)。治疗后,观察组症状评分、肠镜Baron评分、膜屏障功能指标、血清促炎因子、CD8+、FIB、PLT、不良反应发生率较对照组降低(P<0.05),血清抗炎因子、CD3+、CD4+、CD4+/CD8+、NK细胞、APTT升高(P<0.05)。结论加味葛根芩连汤联合常规治疗能有效缓解重度湿热型溃疡性结肠炎患者临床症状,保护肠黏膜,降低不良反应,其机制可能与抑制促炎因子分泌、促进抗炎因子分泌、激活免疫功能、改善凝血功能有关。     

Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass

BackgroundBariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB.MethodsEight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology.ResultsEnrollment body mass index was 49±3 kg/m² (X±SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3–12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months.ConclusionThe early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. β-cell sensitivity improves at 12 months and after the loss of ≈33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and β-cell and L-cell (GLP-1) responses.     

Inferior tarsal muscle-conjunctivectomy for reverse ptosis repair: A novel technique

We describe a new technique for treatment of reverse ptosis in a patient with Horner Syndrome by means of excision of conjunctiva and inferior tarsal muscle. Surgery with eversion of inferior ptotic eyelid, placement of the Putterman ptosis clamp on the conjunctiva under inferior tarsus, suturing under incarcerated tissue and resection of 6mm of conjunctiva and inferior tarsal muscle was done under local anaesthesia in a short operating time with good cosmetic results without eyelid malposition or skin scar.     

A novel technique of Roux-en-Y gastric bypass reversal for postprandial hyperinsulinemic hypoglycaemia: A case report

BackgroundWe describe an evaluation of the effects of partial Roux-en-Y gastric bypass (RYGB) reversal on postprandial hyperinsulinaemic hypoglycaemia, insulin and GLP-1 levels.Case summaryA 37 year old man was admitted with neuroglycopenia (plasma–glucose 1.6 mmol/l) 18 months after RYGB, with normal 72 h fasting test and abdominal CT. Despite dietary modifications and medical treatment, the hypoglycaemic episodes escalated in frequency. Feeding by a gastrostomy tube positioned in the gastric remnant did not prevent severe episodes of hypoglycaemia. A modified reversal of the RYGB was performed. Mixed meal tests were done perorally (PO), through the gastrostomy tube 1 (GT1), 4 weeks (GT2) after placement and 4 weeks after reversal (POr), with assessment of glucose, insulin and GLP-1 levels.ResultsPlasma–glucose increased to a maximum of 9.6, 5.4, 6.5 and 5.8 mmol/l at the PO, GT1, GT2 and POr tests respectively. The corresponding insulin levels were 2939, 731, 725 and 463 pmol/l. A decrease of plasma–glucose followed: 2.2, 3.0, 3.9 and 2.9 mmol/l respectively and insulin levels were suppressed at 150 min: 45, 22, 21 and 14 pmol/l, respectively. GLP-1 levels increased in the PO test (60 min: 122 pmol/l, 21 fold of basal), but was attenuated in the two latter tests (12–23 pmol/l at 60 min).ConclusionsReduction of plasma–glucose, insulin and GLP-1 excursions and symptoms were seen after gastric tube placement and partial RYGB reversal. This attenuation of GLP-1 response to feeding could reflect an adaptation to nutrients.     

骨形态发生蛋白2及碱性成纤维生长因子2对大鼠骨髓间充质干细胞膜片增殖和成骨分化的影响

文题释义： 细胞膜片技术：是在体外接种培养高密度的细胞，使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞，因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点，已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。 成骨细胞：主要由内外骨膜和间充质始祖细胞分化而来，在复杂的骨形成过程中发挥着主要的功能，承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能，能定向分化为成骨细胞，其成骨分化过程可受多种因素的影响，如细胞因子的调控、遗传因素和激素水平等。背景：现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知，如何将生长因子与组织工程细胞膜片技术相整合，最终将其用于骨缺损修复具有重要意义。 目的：探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。 方法：体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片，选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片，CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度；然后对骨髓间充质干细胞膜片进行成骨诱导，通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。 结果与结论：单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性，最佳质量浓度为100 μg/L(P < 0.001)，单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖，最佳质量浓度为20 μg/L(P < 0.001)，而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001)；经成骨诱导后，4组膜片在形态学上无明显差异，均能诱导骨髓间充质干细胞膜片的成骨分化，其中联合组钙结节最明显(P < 0.001)，可显著促进膜片晚期成骨分化并抑制其早期成骨分化，具有明显的协同促进作用(P < 0.001)。结果表明，骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用，既可以促进骨髓间充质干细胞膜片增殖，又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程     

Ideal,catch, and slip bonds in cadherin adhesion

Classical cadherin cell-cell adhesion proteins play key morphogenetic roles during development and are essential for maintaining tissue integrity in multicellular organisms. Classical cadherins bind in two distinct conformations, X-dimer and strand-swap dimer; during cellular rearrangements, these adhesive states are exposed to mechanical stress. However, the molecular mechanisms by which cadherins resist tensile force and the pathway by which they convert between different conformations are unclear. Here, we use single molecule force measurements with an atomic force microscope (AFM) to show that E-cadherin, a prototypical classical cadherin, forms three types of adhesive bonds: catch bonds, which become longer lived in the presence of tensile force; slip bonds, which become shorter lived when pulled; and ideal bonds that are insensitive to mechanical stress. We show that X-dimers form catch bonds, whereas strand-swap dimers form slip bonds. Our data suggests that ideal bonds are formed as X-dimers convert to strand-swap binding. Catch, slip, and ideal bonds allow cadherins to withstand tensile force and tune the mechanical properties of adhesive junctions.     

促甲状腺激素释放激素对结肠平滑肌钾电流的影响

目的探讨促甲状腺激素释放激素(TRH)对大鼠结肠平滑肌细胞膜瞬时外向钾电流(Ito)和延迟整流钾电流(Ik)的影响。方法酶解法急性分离单个大鼠结肠平滑肌细胞,运用膜片钳方法检测10、20、50、100μmol/L的TRH对结肠平滑肌细胞膜Ito和Ik的影响。结果 TRH浓度依赖性减少Ito(P<0.05),10、20、50、100μmol/L的TRH可使峰值Ito降低13.4%、28.0%、39.5%、53.4%,但Ik降低不明显(P>0.05)。结论 TRH阻滞大鼠结肠平滑肌细胞的瞬时外向钾电流,但不能降低延迟整流钾电流,TRH可能通过调节细胞的兴奋性对肠道动力产生影响。